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Journal of Ultrasound in Medicine, Vol 15, Issue 8 577-584, Copyright © 1996 by American Institute of Ultrasound in Medicine
Interaction of diagnostic ultrasound with synthetic oligonucleotide-labeled perfluorocarbon-exposed sonicated dextrose albumin microbubbles
T. R. Porter, P. L. Iversen, S. Li and F. Xie
University of Nebraska Medical Center, Omaha, USA.
The purpose of this study was to determine, first, whether the albumin on
perfluorocarbon-exposed sonicated dextrose albumin microbubbles has
retained its known ability to bind antisense oligonucleotides (DNA utilized
to inhibit viral replication and intimal hyperplasia). The binding kinetics
of synthetic antisense oligonucleotides to perfluorocarbon-exposed
sonicated dextrose albumin microbubbles as well as to room air-containing
sonicated dextrose albumin microbubbles were compared. Second, the effect
of diagnostic ultrasound on this binding is unknown. The ability of
diagnostic ultrasound to release synthetic antisense oligonucleotides from
perfluorocarbon-exposed sonicated dextrose albumin microbubbles also was
tested in vitro and in vivo in three dogs. Synthetic antisense
oligonucleotides exhibited binding to perfluorocarbon-exposed sonicated
dextrose albumin microbubbles much like that of native albumin but did not
bind uniformly with room air-containing sonicated dextrose albumin
microbubbles. Diagnostic ultrasound resulted in significant partitioning of
synthetic antisense oligonucleotides into non-bubble containing regions
after insonation in vitro as well as deposition of greater amounts of
synthetic antisense oligonucleotides in the insonated kidney after
intravenous injections of synthetic anti-sense oligonucleotide-labeled
perfluorocarbon-exposed sonicated dextrose albumin microbubbles. We
conclude that perfluorocarbon-exposed sonicated dextrose albumin
microbubbles, unlike room air-containing sonicated dextrose albumin
microbubbles, have bioactive albumin on their surface that can bind
synthetic antisense oligonucleotides and then release them in the presence
of diagnostic ultrasound.
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